Anthracene oil

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.39 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: DNEL(worker, inhalation, systemic, long-term) is derived from a human oral TDI value (general population) for phenanthrene (see below under 'Discussion/Additional information - worker')

Overall assessment factor (AF):

0.029

Dose descriptor starting point:

other: TDI(oral)

Value:

0.04 mg/kg bw/day

Modified dose descriptor starting point:

other: TCA

Value:

0.07 mg/m³

Explanation for the modification of the dose descriptor starting point:

As starting point for the DNEL(worker, inhalation, systemic, long-term), the original (oral) TDI value (0.04 mg/kg bw/day) for phenanthrene is converted (route-to-route extrapolation) into a TCA value (tolerable concentration in air) taking into account the human standard body weight and the daily respiratory volume (general population). For differences in gastrointestinal and respiratory absorption, a correction factor of 0.5 is allowed for. The TCA is calculated to be 0.07 mg/m³ (0.04 x 70/20 x 0.5/1).

AF for dose response relationship:

1

Justification:

not required; starting point is based on a valid TDI/TCA value

AF for differences in duration of exposure:

0.117

Justification:

adjustment for differences in exposure conditions between general population and workers: 24 h/d, 7 d/w, 52 w/y, 75 y versus 8 h/d, 5 d/w, 48 w/y, 40 y (AF = 1 / (24/8 x 7/5 x 52/48 x 75/ 40 = 1/8.5313 = 0.1172)

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable; starting point relates to humans

AF for other interspecies differences:

1

Justification:

not applicable; starting point relates to humans

AF for intraspecies differences:

0.25

Justification:

adjustment from general population to workers: intraspecies factor (AF = 1 / (10/5) = 0.5); daily respiratory volume (20 versus 10 m³/day) (AF = 1 / (20/10) = 0.5)

AF for the quality of the whole database:

1

Justification:

no special adjustment

AF for remaining uncertainties:

1

Justification:

no special adjustment

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.39 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: adoption of systemic DNEL

Overall assessment factor (AF):

1

Dose descriptor:

other: DNEL(inhal., long-term, systemic) for anthracene oil

Value:

2.39 mg/m³

AF for dose response relationship:

1

Justification:

already included in dose descriptor

AF for differences in duration of exposure:

1

Justification:

already included in dose descriptor

AF for interspecies differences (allometric scaling):

1

Justification:

already included in dose descriptor

AF for other interspecies differences:

1

Justification:

already included in dose descriptor

AF for intraspecies differences:

1

Justification:

already included in dose descriptor

AF for the quality of the whole database:

1

Justification:

no special adjustment

AF for remaining uncertainties:

1

Justification:

no special adjustment

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: DNEL(worker, dermal, systemic, long-term) is derived from a human oral TDI value (general population) for phenanthrene (see below under 'Discussion/Additional information - worker')

Overall assessment factor (AF):

0.059

Dose descriptor starting point:

other: TDI(oral)

Value:

0.04 mg/kg bw/day

Modified dose descriptor starting point:

other: TDI(dermal)

Value:

0.12 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

As starting point for a worker DNEL (dermal, systemic, long-term), an oral TDI value (0.04 mg/kg bw/day) is available. Toxicokinetic and dermal absorption studies provide evidence that dermal absorption of PAH is much lower than gastro-intestinal absorption (see CSR Chapter 5.1.). As conservative estimate, the dermal absorption is assessed to be lower by a factor of three compared to gastrointestinal absorption. This results in a modified dose descriptor starting point (route-to-route extrapolation) of 0.12 mg/kg bw/day (0.04 x 3 = 0.04 x 100/33.33).

AF for dose response relationship:

1

Justification:

not applicable; starting point is based on a valid TDI value

AF for differences in duration of exposure:

0.117

Justification:

adjustment for differences in exposure conditions between general population and workers: 24 h/d, 7 d/w, 52 w/y, 75 y versus 8 h/d, 5 d/w, 48 w/y, 40 y (AF = 1 / (24/8 x 7/5 x 52/48 x 75/ 40 = 1/8.5313 = 0.1172)

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable: starting point relates to humans

AF for other interspecies differences:

1

Justification:

not applicable: starting point relates to humans

AF for intraspecies differences:

0.5

Justification:

adjustment from general population to workers: intraspecies factor (AF = 1 / (10/5) = 0.5)

AF for the quality of the whole database:

1

Justification:

no special adjustments

AF for remaining uncertainties:

1

Justification:

no special adjustments

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Systemic effects - derivation of DNELs

Anthracene oil (AOL) is a UVCB substance and consists of a complex combination of polycyclic aromatic hydrocarbons. It comprises mainly two- and three-ring aromatic compounds (ca. 50 %, typical concentration) with two-ring aromatics forming the smaller fraction. PAHs with four and more rings are present to a lesser extent (< ca. 10 %, see Chapter 1.). In the EU, anthracene oil is not classified as carcinogenic based on its composition. Benzo[a]pyrene is present in concentrations below 50 ppm and other higher molecular weight PAH with clear experimental evidence for carcinogenicity are not present in AOL. Thus, repeated dose toxicity is assessed based on non-carcinogenic threshold effects.

Repeated-dose toxicity data of anthracene oil itself could not be located. Therefore, data of other substances, e.g. constituents of anthracene oil like phenanthrene and other PAH, are used in order to compensate for this lack of data.

Major constituent of AOL is phenanthrene. It is present in AOL in concentrations of 25 to 31% (typical concentration, composite sample 7). Phenanthrene is considered to be among the PAH with the most pronounced effects resulting from non-carcinogenic repeated-dose toxicity. Therefore, phenanthrene is established as marker substance representative for AOL and is used as supporting substance for repeated-dose toxicity of AOL. Other main constituents of AOL are three- to four-ring PAH.

Sub-chronic/chronic non-carcinogenic and carcinogenic effects of phenanthrene and other PAH have been evaluated by RIVM (National Institute for Public Health and the Environment, Ministry of Health, Welfare and Sport, The Netherlands) in an extensive study (Baars et al. 2001, RIVM Report 711701 025). The authors analysed the sub-chronic/chronic toxicity (non-carcinogenic and carcinogenic effects) of 17 PAH using a variety of sources (RIVM Report, Appendix 4. - Polycyclic aromatic hydrocarbons, pp. 143 ff.). First, PAH having a carcinogenic potential were identified and maximum tolerable risk levels were developed.

Non-carcinogenic toxicity was evaluated following the approach of the US Total Petroleum Hydrocarbon Criteria Working Group (TPHCWG) and the US Agency for Toxic Substances and Disease Registry (ATSDR) (RIVM report, Appendix 7.6. - Total Petroleum Hydrocarbons (TPH), p 280 ff.). In this approach (indicator/surrogate approach), Total Petroleum Hydrocarbons were divided into several fractions that included PAH components covering a limited size range (number of carbon atoms). These fractions were examined regarding available repeated-dose toxicity data. Datasets of individual substances resulting from experimental animal studies were analysed and data of individual compounds or fraction-specific mixtures were combined in order develop human TDI values best characterising the repeated-dose toxicity potential of the respective fraction (TDI = tolerable daily intake - the estimated amount of a chemical that humans can ingest daily during their entire lifetime without resultant adverse health effects). Based on expert judgement, a human TDI value of 0.04 mg/kg bw/day was established for the fraction containing phenanthrene. This value is representative of the whole fraction/mixture. But it is also considered to be an average worst-case estimate for individual components of the mixture with unknown toxicity.

In order to cover all relevant components of anthracene oil, evaluation was extended such that PAH up to pyrene were included (for more details see CSR Chapter 5.6.3. - Summary and discussion of repeated dose toxicity). Following the method described above, a human oral TDI value of 0.04 mg/kg bw/day was established that is valid for phenanthrene, but at the same time is also representative of anthracene oil itself, because main constituents of anthracene oil were taken into account in the derivation of the TDI value.

Systemic long-term DNELs for anthracene oil were derived using this TDI value. As it applies to humans, the TDI value had only to be adjusted, as required/appropriate for different DNELs, by route-to-route extrapolation and/or taking into account different exposure conditions between the general population and workers and intraspecies differences. The adjustment procedure and the values used are specified in the sections of the respective DNELs/hazard conclusions.

References:

Baars et al. 2001, Re-evaluation of human-toxicological maximum permissible levels. RIVM report 711701 025 [http://www.rivm.nl/bibliotheek/rapporten/711701025.pdf]

Janssen and Speijers 1997, Guidance on the derivation of Maximum Permissible Risk levels for human intake of soil. RIVM report 711701 006 [http://www.rivm.nl/bibliotheek/rapporten/711701006.pdf]

Local effects - qualitative risk assessment

For some toxicological endpoints like irritation/corrosion or sensitisation, experimental data do not allow a quantitative hazard/risk characterisation. A DNEL cannot be derived. The resulting hazard/risk has to be characterised by a qualitative categorisation.

Data on irritation and sensitisation could not be identified for anthracene oil. Thus information resulting from the closely structure-related tar oil creosote are used as substitute.

Anthracene oil and creosote are closely structure-related products. They are produced in a similar process (fractionated distillation of coal tar using overlapping conditions). Consequently, composition of both substances is quite similar. Major components are mid-range PAH (naphthalene to pyrene). Individual differences in distillation conditions and in starting material may cause gradual variation in qualitative and quantitative composition. But the nature of constituents and the individual components coincide, and the percentage of single substances is of the same magnitude. Toxicological effects of both substances will approximately be the same. Thus, creosote is used as supporting substance to assess qualitative health hazards related to anthracene oil (skin irritation, skin sensitisation).

The qualitative hazard/risk categorisation is performed according to ECHA guidance document on IR&CSA Part E: Risk Characterisation. This categorisation follows classification of endpoints according to the CLP regulation resulting from experimental data. Hazard categories are allocated based on the classification for specific endpoints as outlined in Table E.3-1, p 32 ff. of the guidance document.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.07 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: DNEL(general population, inhalation, systemic, long-term) is derived from a human oral TDI value (general population) for phenanthrene (see below under 'Discussion/Additional information - General Population')

Overall assessment factor (AF):

1

Dose descriptor starting point:

other: TDI(oral)

Value:

0.04 mg/kg bw/day

Modified dose descriptor starting point:

other: TCA

Value:

0.07 mg/m³

Explanation for the modification of the dose descriptor starting point:

As starting point for the DNEL(general population, inhalation, systemic, long-term), the original (oral) TDI value (0.04 mg/kg bw/day) for phenanthrene is converted (route-to-route extrapolation) into a (inhalation) TCA value (tolerable concentration in air) taking into account the human standard body weight and the daily respiratory volume (general population). For differences in gastrointestinal and respiratory absorption, a correction factor of 0.5 is allowed for. The TCA is calculated to 0.07 mg/m³ (0.04 x 70/20 x 0.5/1).

AF for dose response relationship:

1

Justification:

not required; already included in the dose descriptor

AF for differences in duration of exposure:

1

Justification:

not required; already included in the dose descriptor

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable; starting point relates to humans

AF for other interspecies differences:

1

Justification:

not applicable; starting point relates to humans

AF for intraspecies differences:

1

Justification:

not required; already included in the dose descriptor

AF for the quality of the whole database:

1

Justification:

no special adjustment

AF for remaining uncertainties:

1

Justification:

no special adjustment

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.04 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: DNEL(general population, oral, systemic, long-term) is derived by adoption of a human oral TDI value (general population) for phenanthrene without further modification

Overall assessment factor (AF):

1

Dose descriptor starting point:

other: TDI(oral)

Value:

0.04 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No modification of the dose descriptor starting point required.

AF for dose response relationship:

1

Justification:

not required; dose descriptor is a valid TDI value

AF for differences in duration of exposure:

1

Justification:

not required; dose descriptor (TDI) covers lifelong exposure of the general population

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable: starting point relates to humans

AF for other interspecies differences:

1

Justification:

not applicable: starting point relates to humans

AF for intraspecies differences:

1

Justification:

not required; dose descriptor (TDI) covers the general population

AF for the quality of the whole database:

1

Justification:

no special adjustment

AF for remaining uncertainties:

1

Justification:

no special adjustment

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Long-term effects - derivation of DNELs

The general population is not a target group for exposure to anthracene oil (AOL), as there is no use of anthracene oil in consumer products. Exception is exposure of man via environment (inhalation and oral route). As consequence, DNELs(general population) are derived only for inhalation and oral route, systemic, long-term. Other hazards have not been identified for the general population.

Toxicological basis for deduction of DNELs is the TDI value of 0.04 mg/kg bw/day for phenanthrene established by RIVM. This value is valid for phenanthrene as well as for total anthracene oil (see above under ‘Discussion/Additional information - workers’).

Procedure for the deduction of DNELs(general population) is the same as outlined for workers except that no adaption to the target group was necessary (TDI relates to general population). Assessment factors for duration of exposure, for interspecies differences, and for intraspecies differences are therefore each 1.